| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Yale University School of Medicine and Yale Liver Center, New Haven, CT, USA
2 Harvard Medical School, Boston, MA, USA
3 University of Pennsylvania School of Medicine, Philadelphia, PA, USA
4 Centre de recherche en Rhumatologie et Immunologie, Universite Laval, Sainte-Foy, PQ, Canada
* To whom correspondence should be addressed. E-mail: jonathan.dranoff{at}yale.edu.
Background. Extracellular nucleotides regulate a variety of cellular activities, including proliferation of fibrogenic cells outside of the liver. However the expression of receptors for extracellular nucleotides in hepatic stellate cells (HSC) is unknown. Thus, our Aims were to investigate the expression of mediators of nucleotide signaling in HSC and to determine whether extracellular nucleotides regulate HSC function. Methods. Confocal video microscopy was used to observe nucleotide-induced changes in cytosolic Ca2+ (Ca2+ i) in live HSC. P2Y receptor subtype expression and ecto-nucleotidase expression in quiescent and activated HSC were determined using RT-PCR, Northern blot, immunoblot, and confocal immunofluorescence. Functional ecto-nucleotidase activity was assessed using a colorimetric method. Nucleotide-sensitive procollagen-1 mRNA expression in activated HSC was assessed using real-time RT-PCR. Results. Extracellular ATP increased Ca2+ i in HSC; this was inhibited by the P2 receptor inhibitor suramin. Quiescent HSC expressed the P2Y subtypes P2Y2 and P2Y4 and were activated by ATP and UTP, whereas activated HSC expressed the P2Y subtype P2Y6 and were activated by UDP and ATP. Activated, but not quiescent, HSC expressed the ecto-nucleotidase NTPDase2, Extracellular UDP tripled procollagen-1 mRNA expression in activated HSC, and this was inhibited by the P2Y receptor inhibitor suramin. Conclusions. HSC express functional P2Y receptors and switch the expression of P2Y receptor subtypes upon activation. Moreover, HSC differentially regulate NTPDase expression after activation. Since activation of P2Y receptors in activated HSC regulates procollagen-1 transcription, P2Y receptors may be an attractive target to prevent or treat liver fibrosis.
This article has been cited by other articles:
|
|
 |
|
  J. Yu, E. G. Lavoie, N. Sheung, J. J. Tremblay, J. Sevigny, and J. A. Dranoff IL-6 downregulates transcription of NTPDase2 via specific promoter elements Am J Physiol Gastrointest Liver Physiol, March 1, 2008; 294(3): G748 - G756. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. L. Kolachala, R. Bajaj, M. Chalasani, and S. V. Sitaraman Purinergic receptors in gastrointestinal inflammation Am J Physiol Gastrointest Liver Physiol, February 1, 2008; 294(2): G401 - G410. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L. Friedman Hepatic Stellate Cells: Protean, Multifunctional, and Enigmatic Cells of the Liver Physiol Rev, January 1, 2008; 88(1): 125 - 172. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Burnstock Physiology and Pathophysiology of Purinergic Neurotransmission Physiol Rev, April 1, 2007; 87(2): 659 - 797. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A. Kruglov, P. R. A. V. Correa, G. Arora, J. Yu, M. H. Nathanson, and J. A. Dranoff Molecular basis for calcium signaling in hepatic stellate cells Am J Physiol Gastrointest Liver Physiol, April 1, 2007; 292(4): G975 - G982. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Fausther, J. Lecka, F. Kukulski, S. A. Levesque, J. Pelletier, H. Zimmermann, J. A. Dranoff, and J. Sevigny Cloning, purification, and identification of the liver canalicular ecto-ATPase as NTPDase8 Am J Physiol Gastrointest Liver Physiol, March 1, 2007; 292(3): G785 - G795. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. M. Kunzli, P. O. Berberat, T. Giese, E. Csizmadia, E. Kaczmarek, C. Baker, I. Halaceli, M. W. Buchler, H. Friess, and S. C. Robson Upregulation of CD39/NTPDases and P2 receptors in human pancreatic disease Am J Physiol Gastrointest Liver Physiol, January 1, 2007; 292(1): G223 - G230. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Benitez-Rajal, M.-J. Lorite, A. D. Burt, C. P. Day, and M. G. Thompson Phospholipase D and extracellular signal-regulated kinase in hepatic stellate cells: effects of platelet-derived growth factor and extracellular nucleotides. Am J Physiol Gastrointest Liver Physiol, November 1, 2006; 291(5): G977 - G986. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A. Kruglov, R. A. Nathanson, T. Nguyen, and J. A. Dranoff Secretion of MCP-1/CCL2 by bile duct epithelia induces myofibroblastic transdifferentiation of portal fibroblasts Am J Physiol Gastrointest Liver Physiol, April 1, 2006; 290(4): G765 - G771. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
